Radioterapia hipofracionada pré-operatória com FOLFOX para adenocarcinoma de junção esofágica ou gastroesofágica (PHOX)
Radioterapia hipofracionada pré-operatória com FOLFOX para adenocarcinoma de junção esofágica/gastroesofágica (PHOX)
This phase II trial tests how well preoperative (prior to surgery) radiation therapy with fluorouracil, oxaliplatin, and leucovorin calcium (FOLFOX) works for the treatment of stage I-III esophageal or gastroesophageal junction adenocarcinoma. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Fluorouracil stops cells from making deoxyribonucleic acid (DNA) and it may kill tumor cells. Leucovorin is not a chemotherapy medication but is given in conjunction with chemotherapy. Leucovorin is used with the chemotherapy medication fluorouracil to enhance the effects of the fluorouracil, in other words, to make the drug work better. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It damages the cell's DNA and may kill tumor cells. Giving preoperative hypofractionated radiation with fluorouracil and oxaliplatin may kill more tumor cells in patients with stage I-III esophageal or gastroesophageal junction adenocarcinoma.
Visão geral do estudo
Status
Condições
- Estágio Clínico III Adenocarcinoma da Junção Gastroesofágica AJCC v8
- Adenocarcinoma Esofágico Estágio Clínico I AJCC v8
- Adenocarcinoma Esofágico Estágio Clínico II AJCC v8
- Adenocarcinoma Esofágico Estágio Clínico III AJCC v8
- Estágio Clínico II Adenocarcinoma da Junção Gastroesofágica AJCC v8
- Estágio Clínico I Adenocarcinoma da Junção Gastroesofágica AJCC v8
Intervenção / Tratamento
- Medicamento: Docetaxel
- Medicamento: Fluorouracil
- Procedimento: Biospecimen Collection
- Medicamento: Leucovorin Calcium
- Medicamento: Oxaliplatin
- Radiação: Hypofractionated Radiation Therapy
- Outro: Survey Administration
- Biológico: Durvalumab
- Procedimento: Esophagogastroduodenoscopy
- Procedimento: Computed Tomography
- Procedimento: Endoscopic Ultrasound
- Procedimento: Positron Emission Tomography
Descrição detalhada
PRIMARY OBJECTIVE:
I. To demonstrate non-inferiority of pathologic complete response (pCR) with hypofractionated radiotherapy and concurrent FOLFOX compared to historical controls.
SECONDARY OBJECTIVES:
I. Report targeted acute grade ≥ 3 gastrointestinal (GI) toxicity, per Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.
II. Assess post-operative toxicity for patients undergoing esophagectomy, as determined by the Clavien-Dindo Classification.
III. Analyze patient-reported quality of life, per Functional Assessment of Cancer Therapy- Esophageal (FACT-E).
IV. Determine the financial toxicity of hypofractionated radiotherapy, using Comprehensive Score for Financial Toxicity (COST-FACIT).
V. Report overall survival and progression-free survival. VI. Report long-term toxicity secondary to trimodality therapy. VII. Report event-free survival. VIII. Assess outcomes for patients treated with hypofractionated radiotherapy and FOLFOX but who did not proceed to esophagectomy.
IX. Compare toxicity of chemoradiation between patients receiving proton based versus (vs.) photon-based radiotherapy.
X. Compare clinical outcomes and pCR for patients receiving hypofractioned radiotherapy but different induction chemo (immuno) therapy regimens: no induction vs. fluorouracil, oxaliplatin, leucovorin, docetaxel (FLOT) vs. FLOT + durvalumab.
CORRELATIVE OBJECTIVES:
I. Explore the predictive and prognostic role for circulating tumor DNA in esophageal cancer.
II. Study the utility of whole exome and germline sequencing to predict chemoradiation treatment response.
III. Explore the predictive power of whole exome sequencing regarding chemoradiotherapy toxicity.
IV. Implement whole exome and germline sequencing to personalize immunotherapy in esophageal cancer.
V. Study the predictive and prognostic role of tumor-derived extracellular vesicles in esophageal cancer.
OUTLINE:
INDUCTION CHEMOTHERAPY: Patients receive 5-FU intravenously (IV) over 24 hours on day 1, leucovorin calcium IV over 10-120 minutes on day 1, oxaliplatin IV over 2-6 hours on day 1, and docetaxel IV over 1 hour on day 1 of each cycle. Treatment repeats every 2 weeks for a total of up to 6 cycles in the absence of disease progression or unacceptable toxicity. Eligible patients also receive durvalumab IV over 1 hour every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of FLOT, patients undergo radiation therapy daily for 3 weeks with 2 concurrent cycles of FOLFOX.
FOLFOX: Patients receive oxaliplatin IV over 2-6 hours on day 1, leucovorin calcium IV over 10-120 minutes on day 1, and and fluorouracil IV over 46-48 hours on days 1 and 2. of each cycle. Treatment repeats every 2 weeks for a total of 3 cycles in the absence of disease progression or unacceptable toxicity. Starting at cycle 2, patients undergo radiation therapy daily on Monday through Friday for a total of 15 treatments. Patients undergo esophagogastroduodenoscopy (EGD) and/or endoscopic ultrasound (EUS) during screening and undergo computed tomography (CT)/position emission tomography (PET) scan and CT scan as well as blood and tissue sample collection throughout the study.
After completion of study treatment, patients are followed up at 6,12 and 24 months and then up to 5 years.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 2
Contactos e Locais
Contato de estudo
- Nome: Clinical Trials Referral Office
- Número de telefone: 855-776-0015
- E-mail: mayocliniccancerstudies@mayo.edu
Locais de estudo
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Arizona
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Scottsdale, Arizona, Estados Unidos, 85259
- Ainda não está recrutando
- Mayo Clinic in Arizona
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Contato:
- Clinical Trials Referral Office
- Número de telefone: 855-776-0015
- E-mail: mayocliniccancerstudies@mayo.edu
-
Investigador principal:
- Jonathan B. Ashman, MD, PhD
-
-
Florida
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Jacksonville, Florida, Estados Unidos, 32224-9980
- Ativo, não recrutando
- Mayo Clinic in Florida
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-
Minnesota
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Rochester, Minnesota, Estados Unidos, 55905
- Recrutamento
- Mayo Clinic in Rochester
-
Contato:
- Clinical Trials Referral Office
- Número de telefone: 855-776-0015
- E-mail: mayocliniccancerstudies@mayo.edu
-
Investigador principal:
- Christopher L. Hallemeier, MD
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Age ≥ 18 years
- Histological confirmation of esophageal or gastroesophageal junction adenocarcinoma, American Joint Committee on Cancer (AJCC) 8th edition stage T1-4N0-3M0
- Candidate for trimodality therapy: neoadjuvant chemo (immuno) therapy, chemoradiation, and esophagectomy
- Surgical consultation has confirmed that patient is an appropriate candidate for esophagectomy
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Negative pregnancy test done ≤ 7 days prior to chemotherapy, for women of childbearing potential only
- Ability to provide written informed consent and complete questionnaire(s) by themselves or with assistance
- Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
- Willing to provide blood and tissue samples for correlative research purposes
Exclusion Criteria:
-
Clinical or biopsy-proven distant metastatic disease (AJCC 8th edition stage TanyNanyM1)
-
Cervical or upper esophageal tumor
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Prior chemotherapy or radiotherapy for esophageal cancer or history of radiotherapy to the thorax
-
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgement of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with proper assessment of adverse events
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Receiving any investigational agent which would be considered as a treatment for the primary neoplasm or other active malignancy ≤ 1 year prior to registration that is considered by the investigator to interfere with the current treatment or measurement of outcomes
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Any of the following:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Treatment (FLOT and Radiation and FOLFOX)
Patients received Induction Chemotherapy [FLOT (5-FU/leucovorin/oxaliplatin/docetaxel)] following by radiation therapy daily for 3 weeks with 2 concurrent cycles of FOLFOX per protocol. See detailed description for more information. |
Given IV
Outros nomes:
Given IV
Outros nomes:
Undergo blood sample collection
Outros nomes:
Given IV
Outros nomes:
Given IV
Outros nomes:
Undergo hypofractionated radiation therapy
Outros nomes:
Ancillary studies Given IV
Outros nomes:
Undergo EGD
Outros nomes:
Undergo CT and PET/CT scan
Outros nomes:
Undergo EUS
Outros nomes:
Undergo PET and PET/CT scan
Outros nomes:
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Pathologic complete response
Prazo: Up to 5 years after completion of chemoradiation
|
A single-group design will be used to test whether the proportion is potentially non-inferior, with a non-inferiority proportion (P0) of 0.13 (H0: P ≤ 0.13 versus H1: P > 0.13). |
Up to 5 years after completion of chemoradiation
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Incidence of acute ≥ gastrointestinal (GI) adverse events (AEs)
Prazo: Up to 6 weeks after completion of chemoradiation
|
Report acute grade ≥ 3 GI AEs per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. Will be summarized descriptively. |
Up to 6 weeks after completion of chemoradiation
|
|
Incidence of post operative AEs
Prazo: From surgery up to 6 months after completion of chemoradiation
|
Determined by the Clavien-Dindo Classification. Will be summarized descriptively. |
From surgery up to 6 months after completion of chemoradiation
|
|
Patient-reported quality of life (QOL)
Prazo: Up to 24 months after completion of chemoradiation
|
Per Functional Assessment of Cancer Therapy- Esophageal. Will be assessed over time. Wilcoxon signed-rank tests will be used to calculate p-values. Descriptive statistics and graphical methods will also be used to summarize the data. |
Up to 24 months after completion of chemoradiation
|
|
Financial toxicity
Prazo: Up to 24 months after completion of chemoradiation
|
Financial toxicity will be measured using the COmprehensive Score for financial Toxicity (COST), a patient-reported outcome measure that describes the financial distress experienced by cancer patients. The survey consists of 12 questions, each answered with a 0-4 scale where 0=Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit, and 4=Very much. Results will be reported descriptively and include separate consideration of individual item scores. |
Up to 24 months after completion of chemoradiation
|
|
Overall survival (OS)
Prazo: From study entry to death from any cause, up to 5 years after completion of chemoradiation
|
Will be assessed graphically using the Kaplan-Meier method. Summary statistics will be reported, including medians, 95% confidence intervals, etc. |
From study entry to death from any cause, up to 5 years after completion of chemoradiation
|
|
Progression-free survival (PFS)
Prazo: From study entry to the first of either disease progression or death, up to 5 years after completion chemoradiation
|
Will be assessed graphically using the Kaplan-Meier method. Summary statistics will be reported, including medians, 95% confidence intervals, etc. |
From study entry to the first of either disease progression or death, up to 5 years after completion chemoradiation
|
|
Long-term toxicity secondary to trimodality therapy
Prazo: Up to 5 years after completion of chemoradiation
|
Will be reported descriptively using CTCAE version 5.0 criteria. |
Up to 5 years after completion of chemoradiation
|
|
Event free survival
Prazo: From study entry to the first of either disease progression or recurrence or relapse or death, up to 5 years after completion of chemoradiation
|
Will be assessed graphically using the Kaplan-Meier method. Summary statistics will be reported, including medians, 95% confidence intervals, etc. |
From study entry to the first of either disease progression or recurrence or relapse or death, up to 5 years after completion of chemoradiation
|
|
Outcomes for patients treated with hypofractionated radiotherapy and FOLFOX but who did not proceed to esophagectomy
Prazo: Up to 5 years after completion of chemoradiation
|
OS and PFS will be assess using Kaplan-Meier methodology. Summary statistics will be reported, including medians, 95% confidence intervals, etc. AEs and QOL data will be reported with summary statistics and graphical methods, as appropriate. |
Up to 5 years after completion of chemoradiation
|
|
Toxicity of chemoradiation between patients receiving proton based versus photon-based radiotherapy
Prazo: Up to 5 years after completion of chemoradiation
|
Will be done descriptively, reporting frequencies and percentages between patients. |
Up to 5 years after completion of chemoradiation
|
|
Toxicity of chemoradiation between groups receiving proton based versus photon-based radiotherapy
Prazo: Up to 5 years after completion of chemoradiation
|
Will be done descriptively, reporting toxicity rates between groups using the chi-square test. |
Up to 5 years after completion of chemoradiation
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Christopher L. Hallemeier, MD, Mayo Clinic in Rochester
Publicações e links úteis
Links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Aminoácidos, peptídeos e proteínas
- Proteínas
- Compostos de enxofre
- Produtos químicos orgânicos
- Compostos heterocíclicos, 1 anel
- Compostos heterocíclicos
- Compostos heterocíclicos, 2 anel
- Compostos heterocíclicos, anel fundido
- Técnicas de investigação
- Terapêutica
- Técnicas de laboratório clínico
- Técnicas e procedimentos de diagnóstico
- Diagnóstico
- Procedimentos cirúrgicos, operatórios
- Procedimentos cirúrgicos minimamente invasivos
- Técnicas citológicas
- Biópsia
- Citodiagnóstico
- Hidrocarbonetos
- Cicloparaffinas
- Hidrocarbonetos, aliciclicos
- Hidrocarbonetos, cíclicos
- Terpenos
- Fenômenos físicos
- Enzimas e coenzimas
- Anticorpos
- Imunoglobulinas
- Imunoproteínas
- Proteínas sanguíneas
- Globulinas de soro
- Globulins
- Produtos químicos inorgânicos
- Complexos de coordenação
- Taxóides
- Ciclodecanos
- Diterpenos
- Pirimidinas
- Técnicas de diagnóstico, cirúrgico
- Endoscopia, gastrointestinal
- Técnicas de diagnóstico, sistema digestivo
- Endoscopia
- Procedimentos cirúrgicos do sistema digestivo
- Diagnóstico imagens
- Técnicas de química, analíticas
- Análise de espectro
- Formiltetra -hidrofolatos
- Tetra -hidrofolatos
- Ácido fólico
- Pterins
- Pteridinas
- Uracil
- Pirimidinonas
- Coenzimas
- Isotipos de imunoglobulina
- Sulfetos
- Ânions
- Íons
- Eletrólitos
- Sulfeto de hidrogênio
- Fenômenos eletromagnéticos
- Fenômenos magnéticos
- Radioterapia
- Radiação eletromagnética
- Radiação, ionizando
- Fracionamento da dose, radiação
- Dosagem de radioterapia
- Ultrassonografia
- Biópsia, agulha fina
- Biópsia, agulha
- Biópsia guiada por imagem
- Ultrassonografia, intervencional
- Docetaxel
- Oxaliplatina
- Fluorouracila
- Leucovorina
- Imunoglobulina G
- Radiação
- Manipulação de amostras
- Espectroscopia de ressonância magnética
- durValumab
- Dissulfetos
- Raios X
- Hipofracionamento da dose de radiação
- DeHyDroftorafur
- Endoscopia, sistema digestivo
- Gastroscopia
- Aspiração endoscópica de agulha fina guiada por ultrassom
Outros números de identificação do estudo
- GMROR2241
- 23-001689 (Outro identificador: Mayo Clinic Institutional Review Board)
- NCI-2023-07432 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
- GMROR2241 (Outro identificador: Mayo Clinic Radiation Oncology)
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